Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.
Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.
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DOI：
10.1155/2016/6967396
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发表时间：
2016
影响因子：
--
通讯作者：
Gusang L
中科院分区：
文献类型：
--
作者：
Li K;Gesang L;Dan Z;Gusang L
低氧环境导致肠粘膜屏障(IMB)损伤的分子机制尚不清楚。为了解决这个问题，招募了海拔100 m的汉族人和海拔超过3650 m的藏族人。进行组织学和转录组分析。结果表明，与汉族人相比，藏族人肠粘膜绒毛减少，形态不规则，腺上皮遭到破坏。转录组分析显示有2573个基因表达发生了变化。藏族与汉族相比，1137个基因的表达水平升高，1436个基因的表达水平降低。基因本体论(GO)分析表明，与汉族人相比，藏族人IMB的大部分免疫反应都减弱了。基因芯片显示，与汉族相比，藏族IMB中生长因子受体结合蛋白2(Grb2)、表皮生长因子受体(EGFR)和酪氨酸蛋白磷酸酶非受体11(PTPN11)的表达分别下调25、22和18倍。EGFR、Grb2和PTPN11的下调将减少活性氧的产生，对氧化应激诱导的肠道损伤具有保护作用。因此，转录组分析表明IMB患者通过影响Grb2/EGFR/PTPN11通路对藏族人肠道低氧氧化损伤具有保护作用。
The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.
影响因子：
8.8
作者：
Collingridge DR;Hill SA;Chaplin DJ
通讯作者：
Chaplin DJ